Timothy C. Birdsall, ND - National Director of Naturopathic Medicine and Research, Cancer Treatment Centers of America, Zion, IL.

Transcription

1 A Cross-Over Study of the Effect of a Single Oral Feeding of Medium Chain Triglyceride Oil vs. Canola Oil on Post-Ingestion Plasma Triglyceride Levels in Healthy Men Carlo Calabrese, N.D., M.P.H., Suzzanne Myer, M.S., R.D., Suzanne Munson, M.S., Philip Turet, M.S., Timothy C. Birdsall, N.D. Abstract Due to its unique absorption and metabolism characteristics, medium chain triglyceride (MCT) oil, consisting of fatty acids with 8-12 carbons, has been used therapeutically since the 1950s in the treatment of fat malabsorption, cystic fibrosis, epilepsy, weight control, and to increase exercise performance. Medium chain triglycerides are easily hydrolyzed in the intestines and the fatty acids are transported directly to the liver via the portal venous system, in contrast to long-chain fatty acids (LCFAs), which are incorporated into chylomicrons for transport through the lymphatic system or peripheral circulation. Medium chain fatty acids (MCFAs) do not require carnitine to cross the double mitochondrial membrane of the hepatocyte, thus they quickly enter the mitochondria and undergo rapid beta-oxidation, whereas most LCFAs are packaged into triglycerides in the hepatocyte. In this single-blind, randomized, cross-over study, 20 healthy men ingested a single dose of either 71 g of MCT oil or canola oil. Blood samples were taken at baseline and at hours one through five post-ingestion to compare the effect of a single oral dosing of MCT oil versus canola oil on post-ingestion plasma triglyceride levels. Mean triglyceride values after canola oil increased 47 percent above baseline (p ), while mean triglyceride values after MCT oil decreased 15 percent from baseline (p ), which is consistent with several other studies involving short- and longer-term feeding with MCT oil. The effect of long-term usage of MCT oil on triglycerides is yet to be established. (Altern Med Rev 1999;4(1):23-28) Carlo Calabrese, ND, MPH - Bastyr University Research Institute Correspondence address: Juanita Dr NE, Kenmore WA carlo@bastyr.edu Suzzanne Myer, MS, RD - Bastyr University Nutrition Dept. Suzanne Munson, MS - Bastyr University Nutrition Dept. Phillip Turet, MS - Bastyr University Research Institute. Timothy C. Birdsall, ND - National Director of Naturopathic Medicine and Research, Cancer Treatment Centers of America, Zion, IL Alternative Medicine Review Volume 4, Number Page 23

2 Introduction Medium chain triglyceride (MCT) oil is manufactured from coconut and palm kernel oil, and contains fatty acids with 8-12 carbons. It was first introduced in the 1950s as a well-absorbed, calorically-dense nutrient used to treat patients suffering from impaired absorption of traditional long-chain fats. MCT oil has since been used as a major component of enteral and parenteral nutritional support, in the treatment of cystic fibrosis and fat-induced hyperlipidemia, as part of a ketogenic diet in the treatment of epilepsy, to enhance exercise performance, and to aid in increasing the metabolism for weight control. 1,2 MCT oil has also been found to be useful in controlling diarrhea and fat malabsorption in HIVpositive patients, 3,4 and may have potential as part of a ketogenic diet in slowing tumor growth. 5 Although MCT oil is being used for a variety of clinical conditions and is becoming increasingly popular, questions still remain about the nutritional advantages of this product. Specifically, the scientific literature is not yet conclusive regarding the effect of MCT oil on plasma triglyceride levels. Several studies conducted on human subjects with normal intestinal absorption have shown a hypertriglyceridemic effect in response to MCT feeding. 6-9 Children with malabsorption syndromes 10 or cystic fibrosis 11 experienced slight elevations in triglyceride levels associated with MCT feeding. Patients with acute 12 or chronic renal failure 13 experienced similar changes in triglycerides with MCT- or LCT-containing lipid infusions. MCT oil has been shown to markedly lower triglyceride levels in patients with hyperchylomicronemia. 14,15 Healthy male subjects who were given a single oral load of MCT oil (1 g/kg of body weight) or 48 g of MCT oil in a test meal did not experience significant changes in triglyceride levels. 16,17 The purpose of this single-blind, randomized, cross-over study was to examine and further clarify the blood lipid responses associated with MCT feeding. The primary aim of the study was to compare the effect of a single oral feeding of MCT oil with the effect of a single oral feeding of canola oil on the postingestion plasma triglyceride levels in healthy men. Table 1. Mean Triglyceride Levels and Mean Difference Between Canola and MCT Levels at Each Hour Can Mean Baseline ± ± ± ± ± ± 60.7 MCT Mean 80.4 ± ± ± ± ± ± 31.4 Can - MCT -0.7 ± ± ± ± ± ± 51.4 t value* p - value* % C.I. (-12.1, 10.7) (-8.6, 11.8) (9.2, 40.0) (23.6, 67.1) (22.6, 70.6) (14.1, 70.1) Page 24 Alternative Medicine Review Volume 4, Number

3 Medium Chain Triglyceride Oil Methods Participants: The Institutional Review Board at Bastyr University approved the research plan. Twenty healthy men were recruited for the study, and informed consent was obtained from each participant. Potential participants were screened for the following exclusionary criteria: obesity; cardiovascular disease; liver disease; hypoglycemia; hyperlipidemia; pancreatic disease; thyroid dysfunction; current use of prescription drugs, illegal drugs, and/or tobacco; and history of alcohol and/or drug abuse. Participants had normal fasting plasma triglyceride levels ( mg/ dl), reasonably prominent veins, and no known sensitivity to canola, palm, or MCT oil. Each participant was asked to maintain his current level of exercise and alcohol consumption, and to abstain from recreational drug use during the course of the study, beginning one week prior to the first test day. The mean age of the participants was 26 years, with a range of years. Mean weight and height were 74.9 kg and 179 cm, respectively. On the final testing day, each subject was given an exit questionnaire to complete and return. Materials and procedures: The oils used in the study were Sound Nutrition MCT oil and HAIN canola oil, and were purchased at a local supermarket. Each bottle of MCT oil and each Can - BL Can p - value MCT - BL MCT p - value ± bottle of canola oil had the same lot number. In a cross-over design, participants were randomly assigned (by coin toss) to receive either canola or MCT oil first, with ten subjects receiving canola and ten subjects receiving MCT. After a fasting blood draw, participants ingested 71 g (2.5 oz) of either canola or MCT oil, a dose equivalent to the amount of oil found in a meal consisting of a large order of French fries, a salad with oil-based dressing, and a cookie. Blood samples for determination of plasma triglyceride levels were taken at hours one, two, three, four, and five. Blood samples were collected in tubes containing EDTA, centrifuged on site, and refrigerated until testing was completed for the day. The samples were delivered to LabCorp in Seattle, WA, where Chem-23 screens were performed on each sample. Two weeks later, the procedure was repeated with the oil assignments reversed. Statistical Analysis: Data was entered into a spreadsheet program (Microsoft Excel 7, Microsoft, Inc., Redmond, WA) and exported into SPSS (SPSS Inc., Chicago, IL) for analysis. Statistical analyses consisted of parametric comparison of means tests (t-tests) for triglyceride levels under MCT or canola oil at baseline and up to five hours after Table 2. Mean Change from Baseline at Each Hour ± ± ± ± ± ± ± ± 12.8 < ± 12.4 breaking fast. Paired comparisons were made to assess individual responses to treatment. Data exploration showed the hypotheses of normally distributed triglyceride levels and equal variances between treatment groups (at Alternative Medicine Review Volume 4, Number Page 25

4 Figure 1. Mean absolute triglycerides Plasma Triglycerides BL Time (hrs) *t-values and significance statistics refer to mean differences between canola and MCT values different triglyceride levels) could not be rejected, thus justifying the use of parametric tests. Results : The two fasting samples provided by each participant (one on each test day) were not significantly different. Baseline triglycerides (TG) were not related to final TG levels, i.e., relatively high or low TG levels at baseline did not affect the response to MCT or canola oil. Neither age nor body mass index was related to baseline TG levels. Mean TG levels with each oil and the mean differences between canola and MCT levels at each hour are listed in Table 1. Table 2 lists the mean change from baseline at each hour after the ingestion of either oil. Figure 1 shows the curve of mean TG levels at each hour. Mean canola TG values peaked at hour four (117.2±53.0 mg/dl), with a mean difference from baseline of 37.5±40.4 mg/dl (p ). This represents a 47-percent elevation over baseline TG levels. Mean MCT TG levels were below baseline at each hour, and reached the lowest level at hour three (68.6±33.3 mg/dl), with a mean difference from baseline of 11.8±14.6 mg/dl (p = 0.001). This represents a 15- percent decline in plasma triglycerides from baseline TG levels. The mean difference between canola and MCT plasma triglycerides was greatest at hour four Canola MCT (46.6±44.16 mg/dl, p ), but also statistically significant at hours two (p = 0.001), three (p ), and five (p = 0.001). At hour three following the ingestion of canola oil, 80 percent of the participants experienced an increase in triglycerides compared to baseline. At hour three following the ingestion of MCT oil, 75 percent of the participants experienced a decrease in triglycerides compared to baseline. Fifteen exit questionnaires were returned from 20 participants. Fourteen participants reported significant gastrointestinal side-effects, including cramping and diarrhea, associated with ingestion of oil. Thirteen participants experienced diarrhea after ingestion of MCT oil and four participants experienced diarrhea with canola oil ingestion. Three participants experienced diarrhea with ingestion of both oils. Discussion Due to its unique metabolism, medium chain triglyceride oil has proven to be an important source of energy in a variety of clinical conditions. The purpose of this study was to compare the effect of a single oral feeding of MCT oil with the effect of a single oral feeding of canola oil on the post-ingestion plasma triglyceride levels in healthy men. The results of this study are consistent with several previous studies involving short- and longerterm feeding with MCT oil, and further confirm a hypothesized metabolism of MCT oil The action of pancreatic lipase in the small intestine is enhanced by the relatively Page 26 Alternative Medicine Review Volume 4, Number

5 Medium Chain Triglyceride Oil small molecular weight of MCTs, resulting in rapid and near complete hydrolysis of the fatty acids. Unlike long chain fatty acids (LCFA), free medium chain fatty acids (MCFA) are not incorporated into chylomicrons for transport through the lymphatic system or peripheral circulation, but are transported directly to the liver via the portal venous system. MCFAs do not require carnitine or the activity of the regulated enzyme carnitine palmitoyltransferase I to cross the double mitochondrial membrane of the hepatocyte. As a result, the fatty acids quickly enter the mitochondria and undergo rapid betaoxidation. Whereas, most LCFAs are packaged into triglycerides in the hepatocyte, the liver retains most of the MCFAs it receives for energy production. The rapid oxidation of MCFAs results in an excess of acetyl-coa that can be used in a number of different biochemical pathways, including the Kreb s cycle, ketogenesis, elongation of fatty acids, and synthesis of fatty acids and cholesterol. 1,18 Because long-chain fatty acids from canola oil are incorporated preferentially into triglycerides and transported into the plasma via chylomicrons, an increase in triglyceride levels with canola oil feeding relative to MCT oil is not unexpected. Two studies reporting a hypertriglyceridemic effect associated with MCT feeding support an alternative hypothesis that excess acetyl-coa resulting from the rapid oxidation of MCFAs in the liver is used for fatty acid synthesis or elongation. It has also been suggested MCTs stimulate the release of fatty acids from adipose tissue. 8,9 This potential for increased fatty acid production and/or the release of fatty acids from adipose tissue may explain the increase in plasma triglyceride levels seen in these studies. Therapeutic use of MCT oil has been limited due to the occasional occurrence of mild gastrointestinal (GI) symptoms, including borborygmi, crampy abdominal pain, nausea, and diarrhea, 19,20 which was confirmed in this study and at least two previous clinical trials. 17,21 According to Ledeboer et al, MCT oil significantly accelerates small-bowel transit time compared with that seen in control subjects. 19 This acceleration in small-bowel transit time can cause GI side-effects, especially diarrhea. Reportedly, these symptoms can be ameliorated with proper administration of MCT oil. The oil should be introduced in small amounts, heated to room temperature, diluted with an equal volume of water or fruit juice, and taken slowly. It is recommended that no more than ml of MCT oil be taken at one time, with a maximum of 100 ml administered in a 24-hour period. 20,22 In conclusion, this study shows a single oral feeding of MCT oil has a different effect than a single oral feeding of canola oil on postingestion plasma triglyceride levels in healthy men. Plasma TG levels were elevated 47 percent four hours after ingestion of 71 g of canola oil, while plasma TG levels were 15 percent below baseline three hours after ingestion of MCT oil. The effect of long-term feeding with canola and MCT oil on plasma triglycerides is still to be determined. References 1. Bach AC, Babayan VK. Medium-chain triglycerides: an update. Am J Clin Nutr 1982;36: Berning JR. The role of medium-chain triglycerides in exercise. Intl J Sport Nutr 1996;6: Wanke CA, Pleskow D, Degirolami PC, et al. A medium chain triglyceride-based diet in patients with HIV and chronic diarrhea reduces diarrhea and malabsorption: a prospective, controlled trial. Nutr 1996;12: Craig GB, Darrell BE, Weinsier RL, et al. Decreased fat and nitrogen losses in patients with AIDS receiving medium-chain triglyceride-enriched formula vs those receiving longchain triglyceride-containing formula. J Am Diet Assoc 1997;97: Alternative Medicine Review Volume 4, Number Page 27

6 5. Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 1995;14: Cater NB, Heller HJ, Denke MA. Comparison of the effects of medium-chain triacylglycerols, palm oil, and high oleic acid sunflower oil on plasma triacylglycerol fatty acids and lipid and lipoprotein concentrations in humans. Am J Clin Nutr 1997;65: Uzawa H, Michael G, Wood P, et al. Hyperglyceridemia resulting from intake of medium chain triglycerides. Am J Clin Nutr 1965;15: Hill JO, Peters JC, Swift LL, et al. Changes in blood lipids during six days of overfeeding with medium or long chain triglycerides. J Lipid Res 1990;31: Swift LL, Hill JO, Peters JC, Greene HL. Plasma lipids and lipoproteins during 6 d of maintenance feeding with long-chain, medium-chain, and mixed-chain triglycerides. Am J Clin Nutr 1992;56: Tamir I, Gould S, Fosbrooke AS, Lloyd JK. Serum and adipose tissue lipids in children receiving medium-chain triglyceride diets. Arch Dis Child 1969;44: Kuo P, Huang N. The effect of medium chain triglyceride upon fat absorption and plasma lipid and depot fat of children with cystic fibrosis of the pancreas. J Clin Invest 1965;44: Druml W, Fischer M, Sertal S, et al. Fat elimination in acute renal failure: long-chain vs. medium-chain triglycerides. Am J Clin Nutr 1992;55: Druml W, Fischer M, Pidlich J, Lenz K. Fat elimination in chronic hepatic failure: longchain vs. medium-chain triglycerides. Am J Clin Nutr 1995;61: Furman RH, Howard RP, Brusco OJ, Alaupovic P. Effects of medium chain length triglyceride (MCT) on serum lipids and lipoproteins in familial hyperchylomicronemia (dietary fat-induced lipemia) and dietary carbohydrate-accentuated lipemia. J Lab Clin Med 1965;66: Reisell PK, Mandella PA, Poon-King TM, Hatch FT. Treatment of hypertriglyceridemia. Am J Clin Nutr 1966;19: Tamir I, Grant DB, Fosbrooke ES, et al. Effects of a single oral load of medium-chain triglyceride on serum-lipid and insulin levels in man. J Lipid Res 1968;9: Seaton TB, Welle SL, Warenko MK, Campbell RG. Thermic effect of medium-chain and longchain triglycerides in man. Am J Clin Nutr 1986;44: Kalser MH. Medium chain triglycerides. Adv Intern Med 1971;17: Ledeboer M, Masclee AA, Jansen JB, Lamers CB. Effect of equimolar amounts of long-chain triglycerides and medium-chain triglycerides on small-bowel transit time in humans. J Parenter Enteral Nutr 1995;19: Holt PR. Medium chain triglycerides: a useful adjunct in nutritional therapy. Gastroenterology 1967;53: Hashim SA, Arteaga A, Van Itallie TB. Effect of a saturated medium-chain triglyceride on serum lipids in man. Lancet 1960;1: Ruppin DC, Middleton WR. Clinical use of medium chain triglycerides. Drugs 1980;20: Page 28 Alternative Medicine Review Volume 4, Number